tbuckley/cabot-search huggingface dataset:
AB1434 PREGNANCY AND RHEUMATIC DISEASES – COMBINING BIOLOGICAL MATERIAL AND CLINICAL DATA FOR FUTURE RESEARCH
Authors: I. R. Nilssen, B. Jakobsen, T. T. Pedersen, M. Wallenius
Journal: Annals of the Rheumatic Diseases (2022)

Background Rheumatic diseases affect women in fertile age. There is an increased risk for disease flares and pregnancy complications, especially for patients with systemic rheumatic diseases. Improving knowledge of immunological changes that happen during and after pregnancy in women with rheumatic diseases is of great importance. The Norwegian National Advisory Unit for Pregnancy and Rheumatic Diseases (NKSR) therefore established a biobank in 2012 with material from this patient group. NKSR also administers RevNatus, a nation-wide pregnancy quality register including women with inflammatory rheumatic diseases, with comprehensive clinical data. Objectives To facilitate high quality research by developing a possibility to combine biobank material and comprehensive clinical data. We aim to increase current knowledge in this field, with the ultimate goal of making pregnancies safer for women with rheumatic diseases. Methods The RevNatus biobank is part of the Regional Biobank of Central Norway (Biobank 1 ). Biobank 1 is a research facility established to provide an organizational framework for all research, which involves biological material from patients in any of the public hospitals of the region. The collection of biologic material is approved by the regional committees for medical and health research ethics. Patients are included after having signed a consent form. Blood samples are collected before pregnancy, in each trimester, 6 weeks, 6 months and 12 months postpartum. So far, serum, plasma, buffy-coat and Tempus Blood RNA tubes have been collected. At the same time points when blood samples are collected, clinical data is registered in RevNatus. Serum, plasma, buffy-coat and Tempus Blood RNA tubes from 32 healthy pregnant women have also been collected as control group material. Results 310 donors are so far included in the RevNatus biobank. These include systemic lupus erythematosus (36), rheumatoid arthritis (61), juvenile idiopathic arthritis (40), spondyloarthritis (96), Sjögren’s syndrome (8), granulomatosis with polyangiitis (5), MCTD (5), healthy controls (32) and others (27). Table 1. Number of donors in the biobank at each time point Time point Number of donors Before pregnancy 135 donors 1st trimester 123 donors 2nd trimester 124 donors 3rd trimester 117 donors 6 weeks postpartum 175 donors 6 months postpartum 166 donors 12 months postpartum 129 donors Conclusion Collections of biological samples from pregnant women with rheumatic diseases are hard to come by, and therefore research is scarce. RevNatus with its biobank has the potential to make a substantial impact combining clinical and biological material, and take an important role in further molecular research in the field of rheumatic disease and pregnancy. Disclosure of Interests None declared
AB0036 BUTYRIC ACID SUPPRESSES MIGRATION OF MONOCYTE-DERIVED DENDRITIC CELLS BY INHIBITING MDIA1-MEDICATED ACTIN POLYMERIZATION
Authors: T. Nagamoto, T. Okano, Y. Fujikawa, Y. Ueda, H. Yamada, S. Sendo, J. Saegusa
Journal: Annals of the Rheumatic Diseases (2022)

Background Butyric acid is known to improve chronic inflammation such as inflammatory bowel disease and arthritis [1, 2]. Dendritic cells activate in inflammatory condition, migrate to regional lymph nodes, and activate naive T cells. Objectives In this study, we investigated the effect of butyric acid on the migration ability of monocyte-derived dendritic cells (moDC). Methods Human CD14+ Monocytes were purified by positive selection from PBMC using CD14 magnetic beads. Cells were cultured in the presence of GM-CSF (50 ng/ml) and IL-4 (20 ng/ml) for 5 days. After culturing for 5 days, cells were matured with LPS (1ug/ml) for 24 hours. Butyric acid was administered at different dose or period. Surface antigen on moDC was analyzed by flow cytometry (BD FACS VERSE). Migration assay was performed on Boyden chamber CytoSelect 24-Well Cell Migration Assay (5um). Actin was stained with Alexa Fluor 488 Phalloidin before and after migration assay. After administration with butyric acid assigned to each period and concentration, moDC were lysed for western blot analysis for evaluating signaling. Chemiluminescent signals were detected and calculated by Amersham Imager. Results We demonstrated that butyric acid decreased the CCR7 expression of moDC, which has a key role in DC homing to the lymph nodes and intestinal Peyer’s patches. We also showed that butyric acid decreased the migration ability of moDC. Furthermore, moDCs cultured with butyric acid showed a round shape and poor formation of dendrites and pseudopodia. Then we studied the effect of butyric acid on cytoskeleton, which plays an important role in migration and pseudopodia formation of DCs. Polymerized Actin (F-Actin) staining revealed that butyrate suppressed actin polymerization of moDC in a dose dependent manner. CDC42 works important role of lamellipodia and membrane protrusions. RhoA is upstream of mDia1, and mDia1 was reported to accelerate actin nucleation and elongation. We revealed that butyrate decreased the protein expression of mDia1, RhoA, and CDC42, while beta actin was not downregulated, by Western blot analysis. Our results suggested that butyric acid suppresses migration of moDCs by inhibiting mDia1-medicated actin polymerization. Conclusion Butyric acid suppresses migration of moDCs by inhibiting mDia1-medicated actin polymerization. References [1]Mafalda R Couto 1, Pedro Gonçalves 2, Fernando Magro 3, Fátima Martel, et al. Microbiota-derived butyrate regulates intestinal inflammation: Focus on inflammatory bowel disease Pharmacol Res. 2020 Sep;159:104947. [2]Wenpeng Hui, Dapeng Yu, Zhong Cao, Xiwu Zhao, et al. Butyrate inhibit collagen-induced arthritis via Treg/IL-10/Th17 axis Int Immunopharmacol. 2019 Mar;68:226-233. Disclosure of Interests None declared
AB0855 Comparison of cardiac involvement between ankylosing spondylitis and non-radiographic axial spondylitis
Authors: I. El Mezouar, N. Akasbi, T. Harzy
Journal: Annals of the Rheumatic Diseases (2022)

Background While cardiac involvement is increasingly recognized and investigated in patients with axial spondyloarthritis (axSpA), few studies have investigated the occurrence of cardiac involvement in patients with non-radiographic axial spondyloarthritis (nr- axSpA) in relation to ankylosing spondylitis (AS). Objectives The objectives of the present study are to describe and compare the characteristics of cardiac involvement between AS and axSpA nr patients. Methods A cross-sectional study was conducted in the rheumatology department of the University Hospital of Fes in Morocco, including patients diagnosed as having axial spondyloarthritis according to the ASAS 2010 criteria, for a period of 9 years. Patients were classified as r-axSpA by the presence of radiographic sacroiliitis according to the modified New York criteria and nr-axSpA defined by the presence of sacroiliitis on MRI. Results 375 patients were included in the study. We compared 257 AS to 118 with nr-axSpA. The cohort was predominantly female (54.9%) with a mean age of 46.83 years (S.D. 14.00). AS patients were significantly young (45 vs 50 years), more frequently male (55% vs 22%) and had higher serum inflammatory markers than those with nr-axSpA. Between AS and nr-axSpA groups, arterial hypertension was higher in nr-SpA patients (24.6% versus 14.4%, p = 0.016). While valvulopathy, myocardial infarction, pericarditis and heart failure were higher in AS patients with respectively (8.6% vs 3.4%, p=0.067) (1.6% vs 0.8%, p=0.578) (1.2% versus 0.8%, p = 0.779) (0.4% versus 0%, p = 0.497). However, arrhythmias were similar in AS patients and nr-SpA patients (0.8% versus 0.8%, p = 0.571). Conclusion Cardiac involvement was common in both axSpA populations and similar between AS and nraxSpA except in hypertension where there is a significant difference between the two groups. These results highlight the importance of identifying and managing cardiac involvement in these patients Disclosure of Interests None declared
circFBXO7/miR-96-5p/MTSS1 axis is an important regulator in the Wnt signaling pathway in ovarian cancer
Authors: Mengting Wu, Qiongzi Qiu, Qing Zhou, Jia Li, Juze Yang, Chengcai Zheng, Aoran Luo, Xufan Li, Honghe Zhang, Xiaodong Cheng, Weiguo Lu, Pengyuan Liu, Bingjian Lu, Yan Lu
Journal: Molecular Cancer (2022)

Abstract Background CircRNAs are a novel class of evolutionarily conserved noncoding RNA molecules that form covalently closed continuous loop structures without 5′ caps and 3′ poly(A) tails. Accumulating evidence suggests that circRNAs play important regulatory roles in cancer and are promising biomarkers for cancer diagnosis and prognosis, as well as targets for cancer therapy. In this study, we identify and explore the role of a novel circRNA, circFBXO7, in ovarian cancer. Methods rRNA-depleted RNA-sequencing was performed to identify differentially expressed circRNAs between ovarian cancerous and normal tissues. qRT-PCR and single-molecule RNA in-situ hybridization was used to quantify circFBXO7 expression in tumor tissues. The association of circFBXO7 expression with patient prognosis was evaluated by Kaplan–Meier survival analysis. The biological function of circFBXO7 was also investigated using loss-of-function and gain-of-function assays in vivo and in vitro. Luciferase reporter and TOP/FOP-Flash reporter assays were then conducted together with RNA immunoprecipitation and western blot to assess the circFBXO7/miR-96-5p/MTSS1/Wnt/β-catenin axis. Results circFBXO7 was downregulated in ovarian cancer which was associated with poor prognosis. Biologically, circFBXO7 overexpression significantly suppressed ovarian cancer cell proliferation, migration, and invasion in vitro, and inhibited tumor growth and metastasis in vivo, whereas its knockdown exerted an opposite role. Mechanistically, circFBXO7 functioned as a competing endogenous RNA for miR-96-5p to regulate the expression of MTSS1. Consequently, downregulation of MTSS1 led to excessive accumulation of β-catenin and increased phosphorylation of GSK3β, leading to the translocation of β-catenin to the nucleus, thereby activating the Wnt/β-catenin signaling pathway and ultimately promoting ovarian cancer progression. Conclusions Our findings indicate that circFBXO7 acts as a bone fide tumor suppressor in ovarian cancer and that the circFBXO7/miR-96-5p/MTSS1 axis is an important regulator in the Wnt/β-catenin signaling pathway which may provide a promising target for ovarian cancer therapy.
POS0432 MDSCs IN THE INFLAMMATORY JOINT OF SKG MICE HAVE BOTH T CELL SUPPRESSIVE ABILITY AND OSTEOCLAST DIFFERENTIATION POTENTIAL
Authors: Y. Fujikawa, S. Sendo, T. Nagamoto, Y. Yamamoto, H. Yamada, T. Okano, K. Nishimura, Y. Ueda, J. Saegusa
Journal: Annals of the Rheumatic Diseases (2022)

Background Myeloid-derived suppressor cells (MDSCs) are heterogeneous immature myeloid cells with suppressive functions (1). It is known that MDSCs are expanded in inflammatory sites after migrating from bone marrow (BM) or spleen. Rheumatoid arthritis (RA) is an autoimmune disease characterized as polyarthritis. Although previous reports indicate that MDSCs are increased in BM and spleen of arthritis model mice, detailed analysis of MDSCs in inflammatory joints is limited. Objectives The purpose of this study is to characterize the MDSCs in the joints of autoimmune arthritis. Methods We isolated CD11b + Gr1 + cells as MDSCs from joints (Jo-MDSCs), bone marrow (BM-MDSCs) and spleen (Sp-MDSCs) of arthritis-induced SKG mice, and investigated differential expressed genes (DEGs) among MDSCs from three tissues by microarray expression analysis. Furthermore, we analyzed the suppressive function of each MDSCs by investigating the effect of them on T cell -proliferation and the osteoclast differentiation of each MDSCs stimulated by M-CSF and RANKL. Results Microarray analysis revealed that Jo-MDSCs highly expressed immunosuppressive DEGs ( Pdl1, Arg1, Egr2 and Egr3 ) compared to BM MDSCs or Sp MDSCs. In addition, Jo-MDCSs highly expressed NF-κB non-canonical pathway DEGs ( Nfkb2 and Relb ), which are related to osteoclast differentiation. BM-MDSCs differentiated into osteoclasts but didn’t suppress T cell-proliferation and Sp-MDSCs suppressed T cell-proliferation but didn’t differentiate into osteoclasts. On the other hand, Jo-MDSCs was found to have both functions: T cell suppression and osteoclast differentiation potential. Conclusion Jo-MDSCs have a strong inhibitory effect on T cell proliferation and have the ability osteoclast differentiation potential. References [1]Veglia F, Perego M, Gabrilovich D. Myeloid-derived suppressor cells coming of age. Nat Immunol . 2018;19(2):108–19. Disclosure of Interests None declared.
AB1062 EVALUATION OF THE EFFECTIVENESS OF GOUT THERAPY IN OUTPATIENT PRACTICE
Authors: A. Sarapulova, O. Teplyakova
Journal: Annals of the Rheumatic Diseases (2022)

Background gout is a socially significant pathology, as it affects men of working age and is associated with the development of cardiovascular diseases. Meanwhile, according to studies, most patients with gout do not reach the target values ​​of uric acid (UA). Objectives to evaluate the effectiveness of gout therapy in real clinical practice and to identify factors that improve this indicator. Methods The study included patients with an established diagnosis of gout (according to ACR/EULAR criteria). Depending on the stage of the disease, patients were prescribed symptomatic anti-inflammatory therapy, and urate-lowering therapy (UST) - allopurinol or febuxostat - to reduce the level of UA. The dosage of allopurinol in the first 2 months of admission was 300 mg / day and then adjusted depending on the level of UA, the dosage of febuxostat was 80 mg, adjusted to 120 mg if necessary. To prevent exacerbation, all patients were prescribed colchicine 0.5-1.0 mg/day for up to 6 months. After 2 and 6 months of therapy, the effectiveness of it was assessed. All patients had a conversation about the correction of risk factors (diet, alcohol intake) and recommendation to watch online educational school for patients with gout. Results the average age of 60 patients included in the study was 46.9±9.9 years, the duration of the disease was 8.5±3.4 years, of which 96.7% were men. The mean number of exacerbation per year prior to therapy was 7.8±3.5. After 6 months of therapy, 46.7% of patients noted the absence of gout attacks, the rest - a decrease in the duration of attacks (from 10.4 to 1.6 days on average) and their intensity (the average pain during an attack on the VAS scale decreased from 7.8 points up to 3.9). The average level of UA decreased over 2 months from 541.3±146.8 to 387.4±146.9 µmol/l, and after six months of admission it was 299.6±56.5 µmol/l. The creatinine level did not change significantly and amounted to 104.7±34.9 µmol/l before therapy and 97.5±26.7 µmol/l after 6 months. None of the patients discontinued therapy due to intolerance; one of the patients experienced a slight leukopenia while taking febuxostat, which did not lead to discontinuation of the drug. It should be noted that the majority of the subjects - 56.7% - had previously consulted a rheumatologist, but most of them did not receive permanent therapy. Patients highlighted qualitative information and the effect of treatment as the most important reasons for continuing therapy. Conclusion This study proves that achieving the target level of UA is possible in most patients with gout, leads to a significant reduction in the number of attacks and their severity, requires educational work and patient monitoring. It is important that this work is part of a planned 2-year follow-up of patients with gout in order to determine the long-term effectiveness of therapy. Disclosure of Interests None declared
AB1254 CHALLENGES FACED BY FAMILIES OF CHILDREN WITH JUVENILE IDIOPATHIC ARTHRITIS
Authors: W. Triki, A. Dghaies, H. Ferjani, R. Ben Aissa, D. Ben Nessib, K. Maatallah, D. Kaffel, W. Hamdi
Journal: Annals of the Rheumatic Diseases (2022)

Background Juvenile idiopathic arthritis (JIA) is the most common inflammatory rheumatism of childhood. Diagnostic and therapeutic approaches are difficult for families to sustain with significant psychological and social effect. Objectives The aim of this study is to understand the different challenges faced by families with children suffering from JIA. Methods Parents of children with JIA (according to the International League of Associations for Rheumatology (ILAR)) followed in rheumatology department were asked to complete a survey in order to screen the impact of their children’s disease on their family life. Open-ended questions and directed questions were included. General demographic and clinical information (family history of chronic inflammatory disease, child’s current age, diagnosis and type of JIA and, duration of disease progression) were also collected. Results The study included 24 children with a gender-ratio of 1. The mean age was 12.4 years old [4-16]. The mean duration disease was 4 years with extremes varying from 3 months to 13 years. The frequency of each JIA subset was at follows: polyarticular with rheumatoid factor (n= 2), polyarticular without rheumatoid factor (n=5), psoriatic arthritis (n= 1), enthesitis-related arthritis (n=10) and oligoarthritis (n= 6). Twenty-four parents completed the survey. The mother was the one who answered the questions in 83% of the cases. Other family members with a chronic rheumatic disease were reported in 40% of the families. Parents noted negative impact on their work in 50% of cases (40% missing time from work, 10% changing work schedule) and, significant parental stress, anxiety, and fatigue in 75% of the cases. In 33% of the cases, parents had difficulty getting the required medical care and attention for their child’s illness because of financial issues and 37.5% of them were feeling anxiety regarding diagnosis uncertainty. Parents reported worry about their child’s daily functioning and future in 75% of the cases. They noted psychological impact on the child itself in 58% of the cases and child missing school in 41% of the cases. The most common resources parents used for information were health care professionals in 54.2 % of the cases and 45.8% of them got additional information from online research. Conclusion Parents of children with JIA share common challenges due to their child’s illness including a substantial impact on their work and personal wellness in addition to the psychosocial impact of the disease on the child. Support groups or educational sessions may be needed to provide guidance for these families to cope with disease. Disclosure of Interests None declared
AB1207 RISK FACTORS FOR HIGHER RELAPSE RATE AND/OR PROLONGED GLUCOCORTICOID THERAPY IN POLYMYALGIA RHEUMATICA: MULTICENTRE STUDY IN 185 PATIENTS
Authors: A. Cusa, O. Gut, M. D. R. Maliandi, J. Cavallasca, M. Linarez, J. Got, A. Spinetto, A. Estevez, A. Brigante, A. C. Curti, A. C. Costi, J. L. Velasco Zamora, J. P. Vinicki
Journal: Annals of the Rheumatic Diseases (2022)

Background Glucocorticoids (GC) are the therapeutic mainstay in polymyalgia rheumatica (PMR). However, their adverse effects are of particular concern in elderly patients. Relapses and long-term GC dependency are common. Objectives Assess the risk factors for higher relapse rate and/or prolonged glucocorticoid therapy in 185 PMR patients from Argentina. Methods A multicenter observational study of PMR patients diagnosed according to the Chuang criteria seen at the outpatient clinics at 12 public or private rheumatology units from Argentina between 2006 and 2021 was performed. Patients were followed until permanent remission, lost to follow up, or a maximum of 2 years after diagnosis. Relapse was defined as an exacerbation of PMR symptoms requiring an adjustment of GC dose (≥ 4 mg) occurring at least 1 month after diagnosis. Time to relapse was modeled using the Kaplan-Meier method. Cox regression models were used to evaluate predictors of time to first and subsequent relapses. Results A total of 185 patients were included (69.1% female) with a median age of 71 years (IQR 65-78 years). The median follow-up time was 17.1 months (IQR 6.8-34.7) and the incidence of relapses was 1.2 per 100 persons/month. The median time to relapse was 70.5 months (25th percentile = 14 months). Pain and/or stiffness in shoulder girdle and pelvic girdle together more common ( p = 0.02) in the clinical presentation of patients who relapsed. In univariate analysis, PMR patients with a previous history of dyslipidemia had a lower risk of relapse (HR = 0.55, 95% CI = 0.33-0.94, p = 0.03). Laboratory at time of diagnosis showed that an ESR &gt; 50 mm was found as a risk factor for relapse (HR = 2.50, 95% CI = 1.23-5.10, p = 0.011). Regarding therapy, meprednisone (HR = 2.38, 95% CI = 1.31-4.31, p = 0.004) and high dose GC (HR = 2.35, 95% CI = 1.42-3.87, p = 0.001) had higher risk of relapse. In multivariate analysis, only meprednisone (HR = 2.59, 95% CI = 1.28-5.23, p = 0.008) and high dose of GC (HR = 2.41, 95% CI = 1.19-4.89, p = 0.014) remained the only risk factors for relapse. Conclusion A lower relapse rate than that reported in the literature was observed. Meprednisone and high dose of GC are significant predictors of future relapses. Our results suggest that efforts should be made to minimize initial GC dose and avoid the use of meprednisone as GC of first choice in order to prevent disease relapses. Disclosure of Interests None declared
Guidelines for measuring reactive oxygen species and oxidative damage in cells and in vivo
Authors: Michael P. Murphy, Hülya Bayir, Vsevolod Belousov, Christopher J. Chang, Kelvin J. A. Davies, Michael J. Davies, Tobias P. Dick, Toren Finkel, Henry J. Forman, Yvonne Janssen-Heininger, David Gems, Valerian E. Kagan, Balaraman Kalyanaraman, Nils-Göran Larsson, Ginger L. Milne, Thomas Nyström, Henrik E. Poulsen, Rafael Radi, Holly Van Remmen, Paul T. Schumacker, Paul J. Thornalley, Shinya Toyokuni, Christine C. Winterbourn, Huiyong Yin, Barry Halliwell
Journal: Nature Metabolism (2022)